The present invention relates to radiopharmaceutical products used in the treatment of thyroid diseases. In particular, the present invention relates to sodium iodide .sup.131 I capsules which have increased stability and lower volatility.
The use of .sup.131 I-iodide for the treatment of thyroid disease is known in the prior art. In particular, the administration of millicurie amounts of the .sup.131 I-iodide beta emitting isotope to destroy thyroid tissue is generally accepted as preferable to surgical treatment. This is particularly true when malignant or metastatic processes might be involved. The radioiodide has been effectively supplied in both liquid and capsule form, suitable for oral administration, with the choice between the two apparently based on the preference of the treatment provider.
Because of the highly toxic and volatile nature of iodine, the radioiodide formulations have always presented a relatively high degree of risk to those handling the formulations. To reduce this risk, packages of the .sup.131 I-iodide are generally opened in fume hoods to avoid accidental inhalation of iodine. Further, special storage containers having adsorbent iodine traps are used to ship and store the prepared radioiodide.
The iodide ion itself has no volatility, and therefore, the air-borne spread of radioactivity is believed to be caused by another chemical species. Several species are suspected as the carrier of radioactivity, such a hydriodic acid (HI), hypoiodus acid (HOI), iodine (I.sub.2), and organic derivatives such as methyl iodide. The fact that the volatile component reacts with styrofoam, used in the shipping containers, and forms a relatively permanent bond therewith, indicates that the carrier is iodine (I.sub.2).
Difficulties in determining the radioactive volatility of iodide solutions, is caused by the presence of a second source of radioactivity within the capsules. Xenon-131m is formed by decay of radioiodide, and may be present in amounts generally of less than 1%. This makes volatility measurements somewhat misleading when the total volatility is, below 0.08%. In particular, at total levels below 0.08%, the amount of radioiodide must be quantified by a detector capable of reading the 364 Kev energy of .sup.131 I. This is because the Xenon-131m has an energy of 164 Kev, which interferes with the standard ion chamber readings. When total volatility is above 0.08%, the volatility may be attributed entirely to iodine.
The volatility of 131I Capsules may be controlled and reduced by including stabilizers within the formulation. In particular, antioxidant materials may be included to reduce the reduction of the non-volatile iodide ion to volatile species as noted above. The addition of antioxidants may be easily included in the known automated capsule formulation process as described below.
Capsules of radioiodide may be prepared in therapeutic doses of up to 100 mCi as calibrated approximately one week after manufacture, by using an automated apparatus. Initially, empty gelatin capsules are separated into a shell and a cap. The shell is then filled with a sieved powder which serves as a matrix material. An aqueous radioiodide solution is then dispensed directly onto the sieved powder. The cap is then placed onto the shell, and the completed capsule is pneumatically transferred to an ion chamber for acceptance assay. The acceptance rate is generally high, as the dispensing apparatus can be made to be very accurate. Those capsules that are accepted, are individually packaged in small containers, along with a adsorbent charcoal packet. The containers are then capped with a screw cap, and then placed within lead shielding. The lead shields are further supported in styrofoam packing in the outer shipping carton.
The small containers may be plastic, however, it has been found that the use of glass vials reduces the amount of escaping radioiodide. Further, design improvements to the screw cap and adsorbent charcoal packet can also help to reduce the amount of escaping radioiodide.
The matrix material used in the formation of capsules, is generally chosen for chemical inertness and physiological compatibility, such as disodium phosphate (heptahydrate). When using disodium phosphate (heptahydrate) as the matrix material, following capsule formation as described above, the aqueous loading solution is gradually transported through the walls of the gelatin capsule. This is caused in part by the inability of the heptahydrate salt to absorb more water after the capping of the capsule. The iodide ion is contained in the aqueous solution and thus is also transported through the gelatin capsule. It is believed that the bioavailability of the transported iodide is different from that of the iodide remaining in the capsule.
The iodide which escapes may undergo oxidation upon contact with surrounding air, to a volatile species such as those described above, and particularly to iodine. The use of antioxidants within the aqueous radioiodide solution acts to reduce the oxidation rate and thus reduce volatility. One known antioxidant is sodium bisulfate which has proven effective in reducing the volatility of .sup.131 I capsules. However, such capsules still exhibit volatility at an undesirably high level, on the order of 700 nCi/mCi/day. Another known capsule formulation uses an antioxidant mixture of disodium phosphate with sodium thiosulfate. Capsules using this formulation and having activity levels up to 50 mCi, exhibit a fairly constant volatility of 17 nCi/mCi/day, or 1.7.times.10.sup.-3 %/day.
However, it is still desirable to reduce volatility of .sup.131 I capsules to lower levels, and to increase stability of the capsules, in order to reduce the radiation risks to those who must handle the capsules and packaging associated therewith.